WATER QUALITY

ADVI SORT

CHLORPYRIFOS

CRITERIA RND STRNDflRDS DIVISION
OFFICE OF WRTER REGULATIONS RND STANDARDS

UNITED STATES
ENVIRONMENTAL PROTECTION AGENCY

JUNE 1 3 8 S

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WATER QUALITY ADVISORY
Number 11

CHLOROPYRIFOS

Criteria and Standards Division
Office of Water Regulations and Standards
United States Environmental Protection Agency-

Advisory - Aquatic Life.

No aquatic life advisory is given because publication of a
final ambient water quality criterion document for chloropyrifos
is scheduled for September, 1986.

Advisory - Human Health.

The advisory concentration for chloropyrifos in ambient water
for the protection of human health is estimated to be 62 ug/L
when exposure is assumed to include consumption of 6.5 grams of
contaminated fish only. These concentrations do not take rela-
tive source contributions from other media into account. Care
should be taken in the application of this advisory, with con-
sideration of its derivation, as stated in the attached support
document.

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HUMAN HEALTH EFFECTS
LITERATURE SEARCH AND
DATA EVAULATION FOR
CHLOROPYRIFOS

U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF WATER REGULATIONS AND STANDARDS
CRITERIA AND STANDARDS DIVISION
WASHINGTON, D.C. 20460

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TABLE OF CONTENTS

PAGE

INTRODUCTION 		IV

RELATIVE SOURCE CONTRIBUTION 		1

TOXICOKINETICS 		2

HEALTH EFFECTS 		2

QUANTIFICATION OF TOXICOLOGICAL EFFECTS 		3

REFERENCES 		7

LIST OF TABLES

TABLE I. Water Quality Advisory for Chloropyrifos (ug/L)...	6

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INTRODUCTION

Advisories have been developed to give'the best available
scientific information on the aquatic and human health effects of
chemicals in surface waters. They are issued in cases where
information is needed quickly, but where there is not sufficient
data to calculate national ambient water quality criteria.

An advisory concentration for the protection of human health
can be derived from a number of sources: The Office of Drinking
Water Health Effects Advisories; Acceptable Daily Intake (ADI)
values from EPA; Office of Pesticides and Toxic Substances risk
assessments; Carcinogen Assessment Group (CAG) cancer risk
estimates; risk estimates derived from the open literature; or
othe rsources which will be cited in the support document. The
advisory concentrations derived from these sources will vary in
confidence and usefulness, based on the amount and quality of
data used as well as the assumptions behind the original
estimates. The user is advised to read the background
information carefully before using the advisory concentrations to
determine the strengths or deficiencies of the values given in
the advisory.

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Human Health Section
Water Quality Advisory (Chlorpyrifos)

Identifying the most appropriate set of Advisory numbers (fish
only, water only, fish plus water) requires an appreciation of
several parameters:

(1)	Relative source contribution analysis or all sources of
exposure expressed in percent

(2)	Toxicokinetics or the uptake, distribution, retention,
and metabolism of the pollutant

(3)	Health effects including both non-carcinogenic and car-
cinogenic bioeffects

(4)	Quantification of the toxicological effects

A. Relative Source Contribution

The average ambient water concentration(s) of o, 0-
diethyl 0- (3, 5, 6-trichloro-2-pyridyl) phosphoro-
thioate is not known. It is known, however, that Chlor-
pyrifos is an active ingredient of Dursban and Lorsban
(No 84). Dursban is used to control fire ants, turf and
ornamental plant insects, mosquitoes, cockroaches, ter-
mites, lice and horseflies on cattle (FCH85). Lorsban
is used on corn as a soil insecticide for the control of
rootworms, cutworms, billbugs, wireworms, seed corn
maggots, etc. (FCH85). Agricultural application is via
ground, aerial spray and dust. It would be reasonable
to assume that some percentage of Chlorpyrifos does run
off into streams where aquatic exposure would occur.
Furthermore, should the ambient water be used for human
consumption, the potable water tainted with Chlorpyrifos
would contribute to one's total exposure to the insecti-
cide.

The OPP, EPA has established tolerances for Chlorpyrifos
and its metabolite for several food crops and maximum
residue limits are available via Codex Alimentarius (OPP

84) .

An arbitrary assumption that Chlorpyrifos exposure via
water contributes some 20% of one's exposure will be
made in this Water Quality Advisory to conform to the
same prudent procedure used by the NAS(77) and ODW,
EPA(85). Both the NAS and the ODW arbitrarily assumed
that drinking water is responsible for 20% of one's
total exposure to organic chemicals when other sources
are known to exist qualitatively but not quantitatively.

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B.	Toxicokinetics

Based on human kinetics data, Chlorpyrifos is known to
have a gastrointestinal absorption rate of approximately
70% (No 84). Dermal absorption is much less (1-3%) than
absorption orally. Microsomal enzymes catalyze the
oxidative desulfuration of Chlorpyrifos to form an oxon,
and both Chlorpyrifos and the oxon are rapidly hydro- '
lyzed to 3, 5, 6-trichloro-2-pyridinol (3, 5, 6-TCP).
The average gastrointestinal absorption half-life in
humans is 0.5 hr. and the elimination half-life is
approximately 27 hrs. (No 84). Toxicokinetic data by
The Dow Chemical Company suggest that Chlorpyrifos and
its metabolite, 3, 5, 6-TCP have a low potential to
bioaccumulate in man via repeated low level exposure.
If high concentrations of Chlorpyrifos are ingested
continuously, bioaccumulation may be a possibility.

Bioconcentration factors (BCF) for fish of 450 and 320
via flowing vs. static water tests were conducted by
Kenaga and Goring (80). For this Advisory a bioconcen-
tration factor of 385 will be assumed.

C.	Health Effects

Chlorpyrifos can impact the nervous system. High level
exposures can cause a headache, dizziness, weakness,
atoxia, tiny pupils, twitching, tremors, nausea, slow
heartbeat, pulmonary edema, and sweating (EPA 86).
Continual absorption at intermediate dosages may cause
influenza-like illness which includes such symptoms as
weakness, anorexia, and malaise. At low exposure levels
interference of nerve conduction may be impaired.

A summary of the toxicity by Battelle (85) shows that
50-500 ppm may cause death to humans. The LD50 values
for rats, mice, and guinea pigs range from and 100-500
ppm, respectively.

Chlorpyrifos acts by inhibiting the production of
acetyl-cholinesterase, a necessary chemical in nerve
impulse transmission (EPA 86). Plasma cholinesterase
depression appears to be the best indicator of Chlor-
pyrifos exposure. Plasma cholinesterase depression is
more sensitive than erythrocyte cholinesterase depression
as demonstrated by a recent study by Dow Chemical (No
84) .

This organophosphorothioate insecticide and its princi-
pal metabolite (3, 5, 6-trichloro-2-pyridinol) were
investigated by Nolan et al. (84) in which six healthy
male volunteers were administered first a single oral
dose of 0.5 mg/kg, followed by either a dermal dose of
0.5 or 5.0 mg/kg approximately one month later. Plasma
cholinesterase was depressed to 15% of predose levels by

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the 0.5 mg/kg oral exposure some 12 hours post-exposure.
Normalcy of plasma cholinesterase was reached approxi-
mately one month later. The dermal exposures apparently
did not alter the plasma cholinesterase levels. No
s-ignificant changes in erythrocyte chol inesterase
activity were reported for either the oral or dermal
exposures even though on Day 3 post-exposure the data
showed that the erythrocyte cholinesterase activity was
some 70% of predose levels. Blood Chlorpyrifos concen-
trations were extremely low (<30 ng/ml). Mean blood
concentrations of 3, 5, 6-TCP peaked at 0.93 ug/ml 6
hrs. after ingestion. The metabolite peaked at 0.063
ug/ml 24 hrs. after the 5.0 mg/kg dermal dose. No signs
of toxicity were observed in volunteers administered
either a single 0.5 mg/kg oral dose or the 0.5 or 5
mg/kg dermal dose.

Chlorpyrifos appears not to be carcinogenic since two
studies proved to be negative (OPP 85). This insecti-
cide is not teratogenic at levels up to 25 mg/kg/day
(OPP 85). Furthermore, two reproductive studies (two
generation) have been shown not to produce bioeffects at
least up to 1.2 mg/kg/day. The impact on the nervous
system then should be the focus of any advisory.

D. Quantification of Toxicological Effects

In 1982, OPP, EPA reviewed the toxicological data of two
2-year dog and rat feeding studies (EPA 82). The NOELS
based on rbc cholinesterase activity were 0.1 mg/kg/day.
Using a safety factor of only 10, the human ADI was
calculated to be 0.01 mg/kg/day. For a 70 kg adult, the
ADI could have been calculated to be 0.7 mg/day.

Using a paper by Nolan et al. (84), an ADI of 0.005
mg/kg via a precursor bioeffect of 0.5 mg/kg could be
calculated using a safety factor of 100. In this human
volunteer study, 0.5 mg/kg via one oral exposure caused
a significant depression in plasma, but not erythrocyte
chol inesterase. The ADI for a 70 kg adult then could be
calculated to be 0.35 mg/day.

(0.5 mq/kq)(70 kg)  0.35 mg/day
100 S.F.

In 1972 Coulston et al. reported that 0.1 mg/kg/day for
20 days resulted in a plasma but not erythrocyte choli-
nesterase depression in human volunteers. Furthermore a
level of 0.03 mg/kg/day administered over the two-week
study was found not to influence even the plasma choli-
nesterase level. Applying a safety factor of 10, an ADI
of 0.003 mg/kg/day or 0.210 mg/day for the 70 kg adult
could be calculated. The OPP, EPA calculated an ADI of
0.18 mg/day via using an adult weight of 60 rather than
70 kg.

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(0.03 mq/kg/day)(70 kg) = 0.210 mg/day
10. S.F.

Utilizing human data rather than animal data and
averaging the two ADIs calculated from Nolan et. al.
(84) and that specified by OPP, EPA of 0.35 and 0.21
mg/day, respectively, a consensus ADI of 0.28 mg/day
could be obtained.

Without consideration of other sources of exposure, it
is possible to calculate:	'

a.	Lifetime acceptable level in drinking water via
ADI/2

b.	Lifetime acceptable level in ambient water if
only fish were consumed but the water was not
consumed via ADI/RF

c.	Lifetime acceptable level in which the water
was consumed and the fish living within the
water were consumed at the rate of 0.0065
kg/day via ADI/2

plus 385 (0.0065).

The three values for drinking water only, fish only,
water plus fish are 0.14 mg/L, 0.112 mg/L, and 0.062
mg/L, respectively:

o Drinking water only:

ADI = 0.28 mg/day =0.14 mg/L
2	2 1/day

o Fish only:

ADI = 	0-28 mg/day	= 0.112 mg/L

RF (385 BCF) (0.0065 kg/day)

o Ambient water or fish plus drinking water:

ADI = 	0.28 mg/dav = o 062 mg/L

2 + RF	2 1/day + (385) (0.0065 kg/day)

Since water is arbitrarily assumed to contribute some
20% of man's Chlorpyrifos intake, all initial Advisory
levels should be modified by a factor of five (Table l).
Should other sources of exposure be determined on a
case-by-case basis, values other than 10, 20, and 30
ug/L for fish plus potable, fish only and potable only,
respectively, would be more appropriate.

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Table I

WATER QUALITY ADVISORY FOR CHLORPYRIFOS (ug/L)
Water Use	Relative Source Contribution

No

Yes

Fish plus potable

62

10

Fish only

112

20

Potable only

140

30

It should be remembered that Chlorpyrifos is not the
only chemical known to depress chol-inesterase levels and
possibly inhibit nerve transmission. Should other
pollutants affecting this organ system be present, a
dose-addition analysis of all pollutants affecting the
nervous system via this mechanism should be considered
(EPA 85, La 86). The Water Quality Advisory for Chlor-
pyrifos should be modified accordingly in those circum-
stances.

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References

Ba 85. Battelle. Human Health & Aquatic Life Literature
Search & Data Base Evaluation for Chlorpyrifos. Final
Report to OWRS, EPA.

Co 72. Coulston et al. Final Report on Safety Evaluation &
Metabolic Studies on Dowco 179 (IN151). Inst. Exp.
Pathol. Toxicol., Albany Medical College (as cited by No
84) .

EPA 82. U.S. EPA. Chlorpyrifos: Tolerances & Exemptions
from Tolerances for Pesticide Chemicals in or on Raw
Agricultural Commodities. Vol. 47(116) :25961-25962.

EPA 85. U.S. EPA. Proposed Guidelines for the Health Risk
Assessment of Chemical Mixtures 50(6):1170-1175.

EPA 86. U.S. EPA. Pesticide Tolerances for Chlorpyrifos. 40
CFR Part 180, Vol. 51(53) :9449-9450.

EPA 86. U.S. EPA. Chemical Fact Sheet: Chlorpyrifos.
OPP/WDC.

FCH 85. Farm Chemicals. Farm Chemical Handbook, Willoughby,
Ohio 44094.

La 86. Lappenbusch. Contaminated Drinking Water & Your
Health. 6480 Overlook Drive, Alexandria, Virginia
22312.

No 84. Nolan et al. Chlorpyrifos: Pharmacokinetics in
Human Volunteers. Toxicol. & Appl. Pharm. 73:8-15.

OPP 86. U.S. EPA. Chemical Fact Sheet for Chlorpyrifos.
OPP, EPA.

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